Advantages and disadvantages of GH/IGF-I combination treatment

Growth hormone (GH) is the primary regulator of insulin-like growth factor-I (IGF-I) production in a wide variety of tissues. There is much overlap in the endocrine, metabolic and anabolic effects of GH and IGF-I but both hormones have divergent effects on glucose metabolism, insulin sensitivity and differentiation of prechondrocytes. Theoretically combined administration of GH and IGF-I may be more effective than GH alone or IGF-I alone. Arguments in favor for this are: 1] Clearance of IGF-I may be markedly altered by the co-administration of GH and this will provide sustained actions of IGF-I. 2] Higher serum IGF-I levels are achieved with a combination treatment of GH and IGF-I than with GH treatment alone or IGF-I alone. In addition, combination therapy may have additive or synergistic effects. 3] The combination GH and IGF-I counteracts disadvantageous effects on glucose metabolism of either GH alone or IGF-I alone. 4] GH may exert direct actions on tissues independently from IGF-I. 5] Combination of GH and IGF-I may be more effective in improving tissue IGF-I levels. The combination therapy of GH and IGF-I might be beneficial in growth retardation, in certain specific subgroups of critically ill or catabolic patients and in the treatment of GH-deficient subjects with the metabolic syndrome and/or manifest diabetes. It is at present unknown whether an optimal balance between safety and efficacy can be achieved with the combination therapy of GH and IGF-I, since this combination has been evaluated in only a small number of patient populations and in studies of a relatively short duration. In addition, a disadvantage may be the financial costs of combination therapy of GH and IGF-I. In conclusion, there are many reasons for believing that administration of the combination therapy of GH and IGF-I could have advantages above GH alone or IGF-I alone. However, determination of whether co-administration of GH and IGF-I indeed is superior to either agent alone awaits further study.